Poor health literacy has been recognized as a limiting factor in the elderly’s ability to comprehend written or verbal medication information and also to successfully adhere to medical regimens. The objective of this study was to validate a set of pictograms depicting medication instructions for use among the elderly to support health literacy. Elderly outpatients were recruited in 3 community pharmacies in Canada. One-on-one structured interviews were conducted to assess comprehension of 76 pictograms from the International Pharmaceutical Federation. Comprehension was assessed using transparency testing and pictogram translucency, or the degree to which the pictogram represents the intended message. A total of 135 participants were enrolled in this study, and 76 pictograms were assessed. A total of 50 pictograms achieved more than 67% comprehension. Pictograms depicting precautions and warnings against certain side effects were generally not well understood. Gender, age, and education level all had a significant impact on the interpretation scores of certain individual pictograms. When all pictograms were included, younger males had a significantly higher comprehension score than older females, and participants with a higher level of education provided significantly higher translucency scores. Even when pictograms reached the comprehension threshold set by the International Organization for Standardization in the general populations, only 50 of these pictograms achieved more than 67% comprehension among the elderly, confirming that validation in this subpopulation should be conducted prior to using specific pictograms. Accompanying pictograms with education about these pictograms and important counseling points remains extremely important.